Three to ten percent of all infants are born small for gestational age. Underlying etiologies of intrauterine growth retardation (IUGR) vary from maternal malnutrition to placental "insufficiency" seen in association with maternal hypertension. The normal developing fetus quadruples its protein energy reserves during the last trimester of fetal life; this process may be disrupted in the IUGR pregnancy. The placenta is responsible for the concentrative transfer of amino acids from the maternal to the fetal circulations; glutamine and arginine in particular may play essential roles in the maintenance of a positive fetal nitrogen balance. Glutamine and arginine are the primary substrates of the amino acid transport Systems N and y+ respectively. Our long term goal is the understanding of the complex interplay between IUGR and placental amino acid transport, in particular that mediated by Systems N and y+; in order to achieve this goal clear understanding of the membrane distribution and ontogenic regulation of these transport systems is required. Systems N and y+ transport activities have previously been identified in human placenta; the recent production in our laboratory of monospecific antibodies against these transport proteins, as well as the recent isolation of a cDNA clone to System y+ made available to us for the first time will allow exploration of the molecular mechanisms of placental amino acid transport due to these systems. Proposed experiments include the isolation and complete characterization of microvillus and basal membrane vesicles derived from both term human and rat placenta. Amino acid transport mediated by Systems N and y+ will be defined in these membrane vesicles as well as in reconstituted proteoliposomes. Subsequently, monospecific antibodies will be utilized to identify and quantitate the transport proteins responsible for these activities. System y+ mRNA levels also will be quantitated. Transport activity, actual protein content, and mRNA levels in normal term placenta will be compared to those noted in: 1) placenta derived from premature human pregnancies and 2) placenta derived from human infants born IUGR at term. These studies will define ontogenic expression of these transport systems in the presence and absence of IUGR. The ontogeny of these Systems also will be defined in rat placenta, allowing subsequent examination of amino acid transport, transporter protein content and mRNA expression in two established rat models of intrauterine growth retardation.